Introduction
Multiple sclerosis, a neuroinflammatory disease characterized by demyelinating lesions, often has a relapsing-remitting progression. Environmental factors such as poor sunlight exposure is believed to contribute to the initial development of multiple sclerosis. Low vitamin D levels have also been found to be associated with risk of multiple sclerosis. IFN-β treatment in multiple sclerosis patients is known to modulate vitamin D levels, potentially by decreasing serum cholesterol, which in turn modulates the amount of the vitamin D-precursor 7-DHC.
Study Design
Two large, independent multicenter studies
Objective
To assess the effects of ultraviolet radiation and vitamin D on multiple sclerosis severity and to deduce the role of modulatory factors like medication and photosensitivity associated genotypes.
Patient Population
NationMS cohort:
883 treatment-naïve patients (age: ≥ 18 years) with clinically isolated syndrome or relapsing-remitting multiple sclerosis were included in the study.
BIONAT cohort:
990 multiple sclerosis patients were included in the study.
Assessment Parameters
- Serum vitamin D levels, Multiple sclerosis severity score (MSSS), Expanded disability status scale (EDSS) score
- Association between latitude, vitamin D and clinical severity
Results
- In both the cohorts, lower latitude led to higher vitamin D levels.
- In multiple sclerosis patients receiving IFN-β therapy, no effect of latitude on vitamin D levels was seen.
- These patients also had higher vitamin D levels than therapy-naïve patients.
- In untreated and glatiramer acetate-treated patients, there was an increase of vitamin D with the decrease in latitude.
- MC1R missense variants were strongly linked to an individual’s sensitivity to ultraviolet radiation.
- The T allele of the high-penetrance variant rs1805008 raised the risk of severe reaction to sunlight by 91.5%.
- For carriers of rs1805008:T, the risk for gadolinium (Gd)-enhancing lesions increased by 20.5% for every 1° decrease in latitude.
- A significant enrichment of vitamin D-associated genes was found in CD8 T cells and B cells.
- Type I IFN pathway-associated genes were significantly enriched in CD8 T cells, monocytes and B cells.
In the NationMS cohort,
- Higher vitamin D levels were associated with better MSSS scores and lower disability.
- Higher latitude, lower sunlight were associated with worse MSSS scores.
- Satellite-derived ultraviolet radiation showed a similar relation to latitude with MSSS scores.
- The risk for Gd-enhancing lesions was increased by 8.31% for every 1° increase in latitude.
- Baseline vitamin D was associated with a lower grade of disability accumulation and latitude did not have any significant effect on risk of relapse.
- Every 1 ng/mL of serum vitamin D led to risk reduction of relapse by 1% and lower latitude was associated with significantly lower ΔEDSS.
In the BIONAT cohort,
- Similar to the NationMS cohort, higher vitamin D levels were linked to lower disability.
- However, no such effect of latitude on the MSSS was found which was contributed to IFN-β therapy.
- Higher latitude was associated with a worse MSSS in patients who did not receive IFN- β therapy, while no such effect was seen in those receiving IFN-β therapy.
Conclusion
Moderate sun exposure along with higher serum vitamin D levels may be beneficial for multiple sclerosis patients. However, MC1R variants may have detrimental effects of ultraviolet radiation in sun-sensitive patients.